Gamma delta T lymphocytes regulate the induction and maintenance of oral tolerance.
Gamma delta T lymphocytes regulate the induction and maintenance of oral tolerance.
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DOI：
10.4049/jimmunol.158.8.3610
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发表时间：
1997-04
影响因子：
4.4
通讯作者：
Yong Ke;K. Pearce;J. Lake;H. Ziegler;J. Kapp
中科院分区：
文献类型：
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作者：
Yong Ke;K. Pearce;J. Lake;H. Ziegler;J. Kapp
在几天的时间内口服施用Ag，诱导与CD 8 + T细胞活化相关的耐受状态，所述CD 8 + T细胞可以将无应答性转移至初始同基因宿主。我们先前证明这些T细胞不是CTL前体，并且它们抑制CD 8 + CTL的应答，以及Ab和CD 4 + T细胞应答。口服Ag激活非细胞溶解性CD 8+抑制性T细胞的过程尚不清楚。在这些研究中，我们询问γ δ T细胞的耗竭是否改变了口服耐受的诱导。通过Ab、CD 4+和CD 8 + T细胞反应测量，注射抗δ链Ab（GL 3）下调了γ δ TCR的表达，并抑制了对OVA口服耐受的诱导。GL 3没有激活IL-2分泌，这可以在血清中检测到，也没有诱导上皮内淋巴细胞的IL-2 R表达，这表明GL 3抑制γ δ T细胞的功能，而不是激活它们。这种解释得到了我们的观察结果的支持，即口服Ag不会诱导TCR-δ基因敲除小鼠的耐受性。这些数据表明，γ δ T细胞在口服Ag诱导的耐受性中发挥关键的积极作用。
Oral administration of Ag, over a period of several days, induces a state of tolerance that is associated with activation of CD8+ T cells that can transfer unresponsiveness to naive syngeneic hosts. We previously demonstrated that these T cells are not CTL precursors and that they inhibit responses by CD8+ CTL, as well as Ab and CD4+ T cell responses. Activation of noncytolytic, CD8+ suppressor T cells by oral Ag is a process that is not understood. In these studies, we asked whether depletion of the gamma delta T cells altered induction of oral tolerance. Injection of the anti-delta-chain Ab (GL3) down-modulated the expression of gamma delta TCR and inhibited the induction of oral tolerance to OVA, as measured by Ab, CD4+, and CD8+ T cell responses. GL3 did not activate IL-2 secretion that could be detected in the serum, nor did it induce IL-2R expression by intraepithelial lymphocytes, suggesting that GL3 inhibited the function of gamma delta T cells rather than activating them. This interpretation is supported by our observation that oral administration of Ag did not induce tolerance in TCR-delta knockout mice. These data suggest that gamma delta T cells play a critical, active role in tolerance induced by orally administered Ag.